The urinary protein of a patient bearing a highly malignant brain tumor (astrocytoma, grade IV) was adsorbed selectively on trimethylsilyl-controlled pore glass (TMS-CpG) beads to yield a high molecular weight (HMW) human transforming growth factor (hTGF). The growth factor activity had an approximate Mr of 28,000, similar to that of a high molecular weight form of human EGF (HMW hEGF) previously reported to be present in low concentrations in normal human urine. Following surgical resection of the tumor, no appreciable HMW hTGF activity was detectable in a comparable 48-hour urine collection. HMW hTGF generated a competitive binding curve similar to that of standard small molecular weight hEGF, and parallel to HMW hEGF. In its apparent molecular size, receptor binding, immunologic behavior, and clonogenic activity, the brain tumor-associated HMW hTGF was indistinguishable from HMW hEGF. Thus, rather than being uniquely of glioblastoma tumor cell origin, the HMW TGF/EGF growth factor may reflect a host response to tumor burden. An alpha-type transforming growth factor (TGFAlpha) is produced at high levels by rat embryo cells transformed by the Snyder-Theilen strain of feline sarcoma virus. In addition, a beta-type transforming growth factor is present in conditioned cell culture medium that is independent of cell transformation. This TGFBeta had an approximate Mr of 12,000 and eluted at 37% acetonitrile during high performance liquid chromatography. This extracellular type of TGF activity was also present in conditioned medium of transformation-defective mutant rat cells, and in batch extractions made directly from fetal calf serum alone. Consequently, it may derive from the fetal calf serum component of the medium used for their growth in cell culture.